{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:55:11Z","timestamp":1791910511685,"version":"4.3.4"},"reference-count":122,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T00:00:00Z","timestamp":1666051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81760338"],"award-info":[{"award-number":["81760338"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Myocardial ischemia-reperfusion injury (MIRI) results in the aggravation of myocardial injury caused by rapid recanalization of the ischemic myocardium. In the past few years, there is a growing interest in investigating the complex pathophysiological mechanism of MIRI for the identification of effective targets and drugs to alleviate MIRI. Currently, pyroptosis, a type of inflammatory programmed death, has received greater attention. It is involved in the MIRI development in combination with other mechanisms of MIRI, such as oxidative stress, calcium overload, necroptosis, and apoptosis, thereby forming an intertwined association between different pathways that affect MIRI by regulating common pathway molecules. This review describes the pyroptosis mechanism in MIRI and its relationship with other mechanisms, and also highlights non-coding RNAs and non-cardiomyocytes as regulators of cardiomyocyte pyroptosis by mediating associated pathways or proteins to participate in the initiation and development of MIRI. The research progress on novel small molecule drugs, clinical drugs, traditional Chinese medicine, etc. for regulating pyroptosis can play a crucial role in effective MIRI alleviation. When compared to research on other mature mechanisms, the research studies on pyroptosis in MIRI are inadequate. Although many related protective drugs have been identified, these drugs generally lack clinical applications. It is necessary to further explore and verify these drugs to expand their applications in clinical setting. Early inhibition of MIRI by targeted regulation of pyroptosis is a key concern that needs to be addressed in future studies.<\/jats:p>","DOI":"10.3390\/cells11203271","type":"journal-article","created":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T21:18:02Z","timestamp":1666127882000},"page":"3271","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Research Progress on the Role of Pyroptosis in Myocardial Ischemia-Reperfusion Injury"],"prefix":"10.3390","volume":"11","author":[{"given":"Yang","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang 330000, China"},{"name":"Key Laboratory of Anesthesiology of Jiangxi Province, Nanchang 330000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang 330000, China"},{"name":"Key Laboratory of Anesthesiology of Jiangxi Province, Nanchang 330000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5671-3227","authenticated-orcid":false,"given":"Deju","family":"Zhang","sequence":"additional","affiliation":[{"name":"Food and Nutritional Sciences, School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang 330000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang 330000, China"},{"name":"Key Laboratory of Anesthesiology of Jiangxi Province, Nanchang 330000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4435-8034","authenticated-orcid":false,"given":"Shuchun","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang 330000, China"},{"name":"Key Laboratory of Anesthesiology of Jiangxi Province, Nanchang 330000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1056\/NEJMra1606915","article-title":"Acute Myocardial Infarction","volume":"376","author":"Anderson","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Algoet, M., Janssens, S., Himmelreich, U., Gsell, W., Pusovnik, M., Van den Eynde, J., and Oosterlinck, W. (2022). Myocardial ischemia-reperfusion injury and the influence of inflammation. Trends Cardiovasc. Med., Online ahead of print.","DOI":"10.1016\/j.tcm.2022.02.005"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1056\/NEJMra071667","article-title":"Myocardial reperfusion injury","volume":"357","author":"Yellon","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"209","DOI":"10.4103\/tcmj.tcmj_33_18","article-title":"Clinical manifestations and basic mechanisms of myocardial ischemia\/reperfusion injury","volume":"30","author":"Yang","year":"2018","journal-title":"Tzu-Chi Med. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s00395-016-0558-1","article-title":"9th Hatter Biannual Meeting: Position document on ischaemia\/reperfusion injury, conditioning and the ten commandments of cardioprotection","volume":"111","author":"Bell","year":"2016","journal-title":"Basic Res. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1016\/j.jacc.2015.02.032","article-title":"Evolving therapies for myocardial ischemia\/reperfusion injury","volume":"65","author":"Heusch","year":"2015","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.3892\/ijmm.2014.1716","article-title":"Perspectives on the therapeutic modulation of an alternative cell death, programmed necrosis (review)","volume":"33","author":"Cho","year":"2014","journal-title":"Int. J. Mol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1093\/cvr\/cvv225","article-title":"CIRCUS: A kiss of death for cardioprotection?","volume":"108","author":"Heusch","year":"2015","journal-title":"Cardiovasc. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.tcb.2017.05.005","article-title":"Gasdermins: Effectors of Pyroptosis","volume":"27","author":"Kovacs","year":"2017","journal-title":"Trends Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e12563","DOI":"10.1111\/cpr.12563","article-title":"Role of pyroptosis in cardiovascular disease","volume":"52","author":"Zhaolin","year":"2019","journal-title":"Cell Prolif."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/358167a0","article-title":"Shigella flexneri induces apoptosis in infected macrophages","volume":"358","author":"Zychlinsky","year":"1992","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S0966-842X(00)01936-3","article-title":"Pro-inflammatory programmed cell death","volume":"9","author":"Cookson","year":"2001","journal-title":"Trends Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/s41418-017-0012-4","article-title":"Molecular mechanisms of cell death: Recommendations of the Nomenclature Committee on Cell Death 2018","volume":"25","author":"Galluzzi","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1152\/physrev.00022.2018","article-title":"Fundamental Mechanisms of Regulated Cell Death and Implications for Heart Disease","volume":"99","author":"Amgalan","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3207","DOI":"10.1002\/jcp.29268","article-title":"Emerging insights into molecular mechanisms underlying pyroptosis and functions of inflammasomes in diseases","volume":"235","author":"Lu","year":"2020","journal-title":"J. Cell. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1002\/JLB.MR0318-124R","article-title":"Stressing out the mitochondria: Mechanistic insights into NLRP3 inflammasome activation","volume":"105","author":"Yabal","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1007\/s00011-019-01256-6","article-title":"Neferine inhibits LPS-ATP-induced endothelial cell pyroptosis via regulation of ROS\/NLRP3\/Caspase-1 signaling pathway","volume":"68","author":"Tang","year":"2019","journal-title":"Inflamm. Res"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/nature18629","article-title":"Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores","volume":"535","author":"Liu","year":"2016","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/nature15514","article-title":"Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death","volume":"526","author":"Shi","year":"2015","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"151884","DOI":"10.1016\/j.imbio.2019.11.019","article-title":"Research progresses of molecular mechanism of pyroptosis and its related diseases","volume":"225","author":"Gong","year":"2020","journal-title":"Immunobiology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/s41577-019-0228-2","article-title":"The gasdermins, a protein family executing cell death and inflammation","volume":"20","author":"Broz","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/aps.2015.141","article-title":"Detrimental or beneficial: The role of TRPM2 in ischemia\/reperfusion injury","volume":"37","author":"Zhan","year":"2016","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"74","DOI":"10.4330\/wjc.v10.i9.74","article-title":"Myocardial reperfusion injury and oxidative stress: Therapeutic opportunities","volume":"10","author":"Brito","year":"2018","journal-title":"World J. Cardiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1656450","DOI":"10.1155\/2016\/1656450","article-title":"The Role of Oxidative Stress in Myocardial Ischemia and Reperfusion Injury and Remodeling: Revisited","volume":"2016","author":"Kurian","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"165768","DOI":"10.1016\/j.bbadis.2020.165768","article-title":"Mitochondrial ROS in myocardial ischemia reperfusion and remodeling","volume":"1866","author":"Bugger","year":"2020","journal-title":"Biochim. Et Biophys. Acta. Mol. Basis Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2183026","DOI":"10.1155\/2016\/2183026","article-title":"ROS-Mediated NLRP3 Inflammasome Activation in Brain, Heart, Kidney, and Testis Ischemia\/Reperfusion Injury","volume":"2016","author":"Minutoli","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7853","DOI":"10.1074\/jbc.M808824200","article-title":"Neutralization of interleukin-18 ameliorates ischemia\/reperfusion-induced myocardial injury","volume":"284","author":"Venkatachalam","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1097\/SHK.0b013e318160f215","article-title":"Interleukin 18 in the heart","volume":"30","author":"Wang","year":"2008","journal-title":"Shock"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/s41374-018-0135-3","article-title":"The role of Ca2+ in acid-sensing ion channel 1a-mediated chondrocyte pyroptosis in rat adjuvant arthritis","volume":"99","author":"Wu","year":"2019","journal-title":"Lab. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s10517-021-05216-1","article-title":"Activation of Ca2+\/Calmodulin-Dependent Protein Kinase II (CaMKII) with Lidocaine Provokes Pyroptosis of Glioblastoma Cells","volume":"171","author":"Zhou","year":"2021","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/s41420-021-00404-4","article-title":"IP3R1 regulates Ca2+ transport and pyroptosis through the NLRP3\/Caspase-1 pathway in myocardial ischemia\/reperfusion injury","volume":"7","author":"Mo","year":"2021","journal-title":"Cell Death Discov."},{"key":"ref_32","first-page":"153468","article-title":"Ginsenoside Rb1 ameliorates cardiotoxicity triggered by aconitine via inhibiting calcium overload and pyroptosis","volume":"83","author":"Wang","year":"2021","journal-title":"Phytomed. Int. J. Phytother. Phytopharm."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1038\/s41423-020-00630-3","article-title":"Necroptosis, pyroptosis and apoptosis: An intricate game of cell death","volume":"18","author":"Bertheloot","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1038\/s41586-019-1770-6","article-title":"Caspase-8 is the molecular switch for apoptosis, necroptosis and pyroptosis","volume":"575","author":"Fritsch","year":"2019","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e101638","DOI":"10.15252\/embj.2019101638","article-title":"Extrinsic and intrinsic apoptosis activate pannexin-1 to drive NLRP3 inflammasome assembly","volume":"38","author":"Chen","year":"2019","journal-title":"EMBO J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1126\/science.aau2818","article-title":"Pathogen blockade of TAK1 triggers caspase-8-dependent cleavage of gasdermin D and cell death","volume":"362","author":"Orning","year":"2018","journal-title":"Science"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"E10888","DOI":"10.1073\/pnas.1809548115","article-title":"Caspase-8 induces cleavage of gasdermin D to elicit pyroptosis during Yersinia infection","volume":"115","author":"Sarhan","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2056","DOI":"10.1016\/j.cellsig.2007.05.016","article-title":"Cleavage of RIP3 inactivates its caspase-independent apoptosis pathway by removal of kinase domain","volume":"19","author":"Feng","year":"2007","journal-title":"Cell. Signal."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/s41586-019-1548-x","article-title":"Cleavage of RIPK1 by caspase-8 is crucial for limiting apoptosis and necroptosis","volume":"574","author":"Newton","year":"2019","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.immuni.2013.06.018","article-title":"The pseudokinase MLKL mediates necroptosis via a molecular switch mechanism","volume":"39","author":"Murphy","year":"2013","journal-title":"Immunity"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/s41586-019-1752-8","article-title":"Activity of caspase-8 determines plasticity between cell death pathways","volume":"575","author":"Newton","year":"2019","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.4049\/jimmunol.1302839","article-title":"FADD and caspase-8 mediate priming and activation of the canonical and noncanonical Nlrp3 inflammasomes","volume":"192","author":"Gurung","year":"2014","journal-title":"J. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1016\/j.celrep.2018.10.103","article-title":"The Mitochondrial Apoptotic Effectors BAX\/BAK Activate Caspase-3 and -7 to Trigger NLRP3 Inflammasome and Caspase-8 Driven IL-1\u03b2 Activation","volume":"25","author":"Vince","year":"2018","journal-title":"Cell Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.immuni.2012.01.012","article-title":"Inhibitor of apoptosis proteins limit RIP3 kinase-dependent interleukin-1 activation","volume":"36","author":"Vince","year":"2012","journal-title":"Immunity"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"7515","DOI":"10.1038\/ncomms8515","article-title":"Caspase-8 scaffolding function and MLKL regulate NLRP3 inflammasome activation downstream of TLR3","volume":"6","author":"Kang","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1161\/CIRCULATIONAHA.110.982777","article-title":"Inflammasome activation of cardiac fibroblasts is essential for myocardial ischemia\/reperfusion injury","volume":"123","author":"Kawaguchi","year":"2011","journal-title":"Circulation"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1093\/cvr\/cvt091","article-title":"The NLRP3 inflammasome is up-regulated in cardiac fibroblasts and mediates myocardial ischaemia-reperfusion injury","volume":"99","author":"Sandanger","year":"2013","journal-title":"Cardiovasc. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1093\/cvr\/cvt142","article-title":"NLRP3 in myocardial ischaemia-reperfusion injury: Inflammasome-dependent or -independent role in different cell types","volume":"99","author":"Takahashi","year":"2013","journal-title":"Cardiovasc. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.actbio.2022.02.018","article-title":"Endothelial cell-targeting, ROS-ultrasensitive drug\/siRNA co-delivery nanocomplexes mitigate early-stage neutrophil recruitment for the anti-inflammatory treatment of myocardial ischemia reperfusion injury","volume":"143","author":"Hou","year":"2022","journal-title":"Acta Biomater."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"H179","DOI":"10.1152\/ajpheart.00002.2017","article-title":"Endothelial cAMP deactivates ischemia-reperfusion-induced microvascular hyperpermeability via Rap1-mediated mechanisms","volume":"313","author":"Korayem","year":"2017","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1002\/cbin.11614","article-title":"microRNA-129 overexpression in endothelial cell-derived extracellular vesicle influences inflammatory response caused by myocardial ischemia\/reperfusion injury","volume":"45","author":"Zheng","year":"2021","journal-title":"Cell Biol. Int."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1159\/000493042","article-title":"MicroRNA-495 Ameliorates Cardiac Microvascular Endothelial Cell Injury and Inflammatory Reaction by Suppressing the NLRP3 Inflammasome Signaling Pathway","volume":"49","author":"Zhou","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/s41419-020-02985-x","article-title":"NLRP3 inflammasome in endothelial dysfunction","volume":"11","author":"Bai","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.bbrc.2019.04.143","article-title":"Adiponectin alleviates NLRP3-inflammasome-mediated pyroptosis of aortic endothelial cells by inhibiting FoxO4 in arteriosclerosis","volume":"514","author":"Zhang","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e12072","DOI":"10.1002\/jev2.12072","article-title":"Myocardial ischemia-reperfusion induced cardiac extracellular vesicles harbour proinflammatory features and aggravate heart injury","volume":"10","author":"Ge","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.yjmcc.2020.02.007","article-title":"M2 macrophage-derived exosomes carry microRNA-148a to alleviate myocardial ischemia\/reperfusion injury via inhibiting TXNIP and the TLR4\/NF-\u03baB\/NLRP3 inflammasome signaling pathway","volume":"142","author":"Dai","year":"2020","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.jacc.2018.09.086","article-title":"Multitarget Strategies to Reduce Myocardial Ischemia\/Reperfusion Injury: JACC Review Topic of the Week","volume":"73","author":"Davidson","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/s41420-022-00909-6","article-title":"Mesenchymal stem cell-derived exosomal microRNA-182-5p alleviates myocardial ischemia\/reperfusion injury by targeting GSDMD in mice","volume":"8","author":"Yue","year":"2022","journal-title":"Cell Death Discov."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"105743","DOI":"10.1016\/j.phrs.2021.105743","article-title":"Role of epigenetic regulation in myocardial ischemia\/reperfusion injury","volume":"170","author":"Wang","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"23651","DOI":"10.3390\/ijms161023651","article-title":"Long Non-Coding RNAs as Master Regulators in Cardiovascular Diseases","volume":"16","author":"Archer","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1124\/jpet.119.256982","article-title":"Inhibiting MicroRNA-29a Protects Myocardial Ischemia-Reperfusion Injury by Targeting SIRT1 and Suppressing Oxidative Stress and NLRP3-Mediated Pyroptosis Pathway","volume":"372","author":"Ding","year":"2020","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_62","first-page":"1942","article-title":"MicroRNA-132 promotes oxidative stress-induced pyroptosis by targeting sirtuin 1 in myocardial ischaemia-reperfusion injury","volume":"45","author":"Zhou","year":"2020","journal-title":"Int. J. Mol. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1038\/nm.4179","article-title":"The long noncoding RNA Chaer defines an epigenetic checkpoint in cardiac hypertrophy","volume":"22","author":"Wang","year":"2016","journal-title":"Nat. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.devcel.2019.07.013","article-title":"The lncRNA Locus Handsdown Regulates Cardiac Gene Programs and Is Essential for Early Mouse Development","volume":"50","author":"Ritter","year":"2019","journal-title":"Dev. Cell"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1038\/s41440-022-00884-6","article-title":"LncRNA Rian reduces cardiomyocyte pyroptosis and alleviates myocardial ischemia-reperfusion injury by regulating by the miR-17-5p\/CCND1 axis","volume":"45","author":"Kang","year":"2022","journal-title":"Hypertens. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/s41374-021-00722-2","article-title":"LncRNA ROR modulates myocardial ischemia-reperfusion injury mediated by the miR-185-5p\/CDK6 axis","volume":"102","author":"Sun","year":"2022","journal-title":"Lab. Investig."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"747802","DOI":"10.3389\/fcvm.2021.747802","article-title":"LncRNA PVT1 Knockdown Ameliorates Myocardial Ischemia Reperfusion Damage via Suppressing Gasdermin D-Mediated Pyroptosis in Cardiomyocytes","volume":"8","author":"Li","year":"2021","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/s41576-019-0158-7","article-title":"The biogenesis, biology and characterization of circular RNAs","volume":"20","author":"Kristensen","year":"2019","journal-title":"Nat. Rev. Genet."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"8590861","DOI":"10.1155\/2020\/8590861","article-title":"CircANXA2 Promotes Myocardial Apoptosis in Myocardial Ischemia-Reperfusion Injury via Inhibiting miRNA-133 Expression","volume":"2020","author":"Zong","year":"2020","journal-title":"BioMed Res. Int."},{"key":"ref_70","first-page":"10107","article-title":"CircHIPK3 aggravates myocardial ischemia-reperfusion injury by binding to miRNA-124-3p","volume":"23","author":"Bai","year":"2019","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_71","first-page":"6323","article-title":"Circ-100338 induces angiogenesis after myocardial ischemia-reperfusion injury by sponging miR-200a-3p","volume":"24","author":"Chang","year":"2020","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1038\/s41420-021-00706-7","article-title":"CircRNA circ-NNT mediates myocardial ischemia\/reperfusion injury through activating pyroptosis by sponging miR-33a-5p and regulating USP46 expression","volume":"7","author":"Ye","year":"2021","journal-title":"Cell Death Discov."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"106768","DOI":"10.1016\/j.intimp.2020.106768","article-title":"Dexmedetomidine inhibits pyroptosis by down-regulating miR-29b in myocardial ischemia reperfusion injury in rats","volume":"86","author":"Zhong","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1111\/jcmm.15953","article-title":"Piperine protects against pyroptosis in myocardial ischaemia\/reperfusion injury by regulating the miR-383\/RP105\/AKT signalling pathway","volume":"25","author":"Guo","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nm.3806","article-title":"A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases","volume":"21","author":"Coll","year":"2015","journal-title":"Nat. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s10753-019-01098-8","article-title":"Target of MCC950 in Inhibition of NLRP3 Inflammasome Activation: A Literature Review","volume":"43","author":"Wu","year":"2020","journal-title":"Inflammation"},{"key":"ref_77","first-page":"828","article-title":"The selective NLRP3-inflammasome inhibitor MCC950 reduces infarct size and preserves cardiac function in a pig model of myocardial infarction","volume":"38","author":"Bosch","year":"2017","journal-title":"Eur. Heart J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5271251","DOI":"10.1155\/2016\/5271251","article-title":"Pharmacological Inhibition of NLRP3 Inflammasome Attenuates Myocardial Ischemia\/Reperfusion Injury by Activation of RISK and Mitochondrial Pathways","volume":"2016","author":"Mastrocola","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"107358","DOI":"10.1016\/j.intimp.2020.107358","article-title":"NLRP3 inflammasome inhibitor INF39 attenuated NLRP3 assembly in macrophages","volume":"92","author":"Shi","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1007\/s00395-018-0692-z","article-title":"Caspase-1 inhibition by VX-765 administered at reperfusion in P2Y(12) receptor antagonist-treated rats provides long-term reduction in myocardial infarct size and preservation of ventricular function","volume":"113","author":"Audia","year":"2018","journal-title":"Basic Res. Cardiol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1080\/14656566.2020.1787987","article-title":"Targeted pharmacotherapy for ischemia reperfusion injury in acute myocardial infarction","volume":"21","author":"Rout","year":"2020","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s10557-018-6781-2","article-title":"The Caspase 1 Inhibitor VX-765 Protects the Isolated Rat Heart via the RISK Pathway","volume":"32","author":"Arjun","year":"2018","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1007\/s00395-017-0662-x","article-title":"The RISK pathway and beyond","volume":"113","author":"Rossello","year":"2018","journal-title":"Basic Res. Cardiol."},{"key":"ref_84","first-page":"61","article-title":"Colchicine in Cardiovascular Disease: In-Depth Review","volume":"145","author":"Deftereos","year":"2022","journal-title":"Circulation"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1093\/ehjqcco\/qcaa045","article-title":"Cost-effectiveness of low-dose colchicine after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT)","volume":"7","author":"Samuel","year":"2021","journal-title":"Eur. Heart J. Qual. Care Clin. Outcomes"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1056\/NEJMoa1912388","article-title":"Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction","volume":"381","author":"Tardif","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1177\/1074248418763611","article-title":"Cardioprotective Role of Colchicine Against Inflammatory Injury in a Rat Model of Acute Myocardial Infarction","volume":"23","author":"Bakhta","year":"2018","journal-title":"J. Cardiovasc. Pharmacol. Ther."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"804030","DOI":"10.3389\/fphar.2021.804030","article-title":"Network Pharmacology-Based Investigation and Experimental Exploration of the Antiapoptotic Mechanism of Colchicine on Myocardial Ischemia Reperfusion Injury","volume":"12","author":"Tang","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"Fso656","DOI":"10.2144\/fsoa-2020-0151","article-title":"Low-dose colchicine prevents sympathetic denervation after myocardial ischemia-reperfusion: A new potential protective mechanism","volume":"7","author":"Huet","year":"2020","journal-title":"Future Sci. OA"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.ijcard.2017.03.126","article-title":"Interest of colchicine in the treatment of acute myocardial infarct responsible for heart failure in a mouse model","volume":"240","author":"Akodad","year":"2017","journal-title":"Int. J. Cardiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"660698","DOI":"10.3389\/fcvm.2021.660698","article-title":"Myocardial Ischemia-Reperfusion and Diabetes: Lessons Learned From Bedside to Bench","volume":"8","author":"Dia","year":"2021","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"101534","DOI":"10.1016\/j.redox.2020.101534","article-title":"Metformin protects against intestinal ischemia-reperfusion injury and cell pyroptosis via TXNIP-NLRP3-GSDMD pathway","volume":"32","author":"Jia","year":"2020","journal-title":"Redox Biol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"8768327","DOI":"10.1155\/2019\/8768327","article-title":"Metformin Protects against Oxidative Stress Injury Induced by Ischemia\/Reperfusion via Regulation of the lncRNA-H19\/miR-148a-3p\/Rock2 Axis","volume":"2019","author":"Zeng","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1111\/cts.12846","article-title":"Metformin Preconditioning and Postconditioning to Reduce Ischemia Reperfusion Injury in an Isolated Ex Vivo Rat and Porcine Kidney Normothermic Machine Perfusion Model","volume":"14","author":"Huijink","year":"2021","journal-title":"Clin. Transl. Sci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"285","DOI":"10.5213\/inj.2142206.103","article-title":"Metformin and Sildenafil Attenuate Inflammation and Suppress Apoptosis After Ischemia\/Reperfusion Injuries in Rat Urinary Bladder","volume":"25","author":"Park","year":"2021","journal-title":"Int. Neurourol. J."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e410.e1","DOI":"10.1016\/j.jpurol.2016.06.017","article-title":"Effects of melatonin and metformin co-administration on testicular ischemia\/reperfusion injury in rats","volume":"12","author":"Asghari","year":"2016","journal-title":"J. Pediatric Urol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.tjog.2020.10.004","article-title":"Metformin reduces ovarian ischemia reperfusion injury in rats by improving oxidative\/nitrosative stress","volume":"60","author":"Demir","year":"2021","journal-title":"Taiwan. J. Obstet. Gynecol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"6437467","DOI":"10.1155\/2017\/6437467","article-title":"Insights for Oxidative Stress and mTOR Signaling in Myocardial Ischemia\/Reperfusion Injury under Diabetes","volume":"2017","author":"Zhao","year":"2017","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.lfs.2019.04.002","article-title":"Metformin promotes autophagy in ischemia\/reperfusion myocardium via cytoplasmic AMPK\u03b11 and nuclear AMPK\u03b12 pathways","volume":"225","author":"Wang","year":"2019","journal-title":"Life Sci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"196","DOI":"10.2174\/1871530315666150316124019","article-title":"Metformin and Inflammation: Its Potential Beyond Glucose-lowering Effect","volume":"15","author":"Saisho","year":"2015","journal-title":"Endocr. Metab. Immune Disord. Drug Targets"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"C873","DOI":"10.1152\/ajpcell.00604.2020","article-title":"The intersection of metformin and inflammation","volume":"320","author":"Bharath","year":"2021","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.metabol.2018.03.004","article-title":"Activation of AMPK inhibits inflammatory response during hypoxia and reoxygenation through modulating JNK-mediated NF-\u03baB pathway","volume":"83","author":"Chen","year":"2018","journal-title":"Metabolism"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"24270","DOI":"10.18632\/aging.202143","article-title":"Metformin protects against myocardial ischemia-reperfusion injury and cell pyroptosis via AMPK\/NLRP3 inflammasome pathway","volume":"12","author":"Zhang","year":"2020","journal-title":"Aging"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1097\/SHK.0b013e318254d3fb","article-title":"Direct protective effects of dexmedetomidine against myocardial ischemia-reperfusion injury in anesthetized pigs","volume":"38","author":"Yoshitomi","year":"2012","journal-title":"Shock"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1213\/ANE.0000000000002452","article-title":"Dexmedetomidine Maintains Its Direct Cardioprotective Effect Against Ischemia\/Reperfusion Injury in Hypertensive Hypertrophied Myocardium","volume":"126","author":"Yoshikawa","year":"2018","journal-title":"Anesth. Analg."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.ijcard.2019.05.063","article-title":"Trimetazidine in cardiovascular medicine","volume":"293","author":"Marzilli","year":"2019","journal-title":"Int. J. Cardiol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1016\/S0140-6736(20)31790-6","article-title":"Efficacy and safety of trimetazidine after percutaneous coronary intervention (ATPCI): A randomised, double-blind, placebo-controlled trial","volume":"396","author":"Ferrari","year":"2020","journal-title":"Lancet"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/s00011-021-01530-6","article-title":"Trimetazidine affects pyroptosis by targeting GSDMD in myocardial ischemia\/reperfusion injury","volume":"71","author":"Chen","year":"2022","journal-title":"Inflamm. Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"975","DOI":"10.2147\/DDDT.S195412","article-title":"Emodin alleviates myocardial ischemia\/reperfusion injury by inhibiting gasdermin D-mediated pyroptosis in cardiomyocytes","volume":"13","author":"Ye","year":"2019","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"153798","DOI":"10.1016\/j.phymed.2021.153798","article-title":"Cardioprotective activity of ethyl acetate extract of Cinnamomi Ramulus against myocardial ischemia\/reperfusion injury in rats via inhibiting NLRP3 inflammasome activation and pyroptosis","volume":"93","author":"Peng","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s00395-016-0533-x","article-title":"Inhibition of ceramide de novo synthesis as a postischemic strategy to reduce myocardial reperfusion injury","volume":"111","author":"Reforgiato","year":"2016","journal-title":"Basic Res. Cardiol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"986","DOI":"10.3389\/fphys.2019.00986","article-title":"Sphingolipid Synthesis Inhibition by Myriocin Administration Enhances Lipid Consumption and Ameliorates Lipid Response to Myocardial Ischemia Reperfusion Injury","volume":"10","author":"Bonezzi","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"901322","DOI":"10.3389\/fmolb.2022.901322","article-title":"Corrigendum: Sevoflurane Alleviates Myocardial Ischemia Reperfusion Injury by Inhibiting P2X7-NLRP3 Mediated Pyroptosis","volume":"9","author":"Wu","year":"2022","journal-title":"Front. Mol. Biosci."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1161\/ATVBAHA.120.315116","article-title":"P2X7 Receptors: An Untapped Target for the Management of Cardiovascular Disease","volume":"41","author":"Shokoples","year":"2021","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"654425","DOI":"10.3389\/fphar.2021.654425","article-title":"P2X7 Receptor-Mediated Inflammation in Cardiovascular Disease","volume":"12","author":"Zhou","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"353152","DOI":"10.1155\/2012\/353152","article-title":"Molecular hydrogen as an emerging therapeutic medical gas for neurodegenerative and other diseases","volume":"2012","author":"Ohno","year":"2012","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1320365","DOI":"10.1155\/2016\/1320365","article-title":"Hydrogen-Rich Saline Attenuates Cardiac and Hepatic Injury in Doxorubicin Rat Model by Inhibiting Inflammation and Apoptosis","volume":"2016","author":"Gao","year":"2016","journal-title":"Mediat. Inflamm."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.3389\/fphys.2018.01026","article-title":"Inhalation of Hydrogen Attenuates Progression of Chronic Heart Failure via Suppression of Oxidative Stress and P53 Related to Apoptosis Pathway in Rats","volume":"9","author":"Chi","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1016\/j.bbrc.2008.10.156","article-title":"Consumption of hydrogen water prevents atherosclerosis in apolipoprotein E knockout mice","volume":"377","author":"Ohsawa","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1097\/TP.0b013e3181fe1357","article-title":"Inhaled hydrogen gas therapy for prevention of lung transplant-induced ischemia\/reperfusion injury in rats","volume":"90","author":"Kawamura","year":"2010","journal-title":"Transplantation"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.jpedsurg.2011.09.035","article-title":"Inhaled hydrogen gas therapy for prevention of testicular ischemia\/reperfusion injury in rats","volume":"47","author":"Lee","year":"2012","journal-title":"J. Pediatric Surg."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"119248","DOI":"10.1016\/j.lfs.2021.119248","article-title":"Hydrogen gas inhalation alleviates myocardial ischemia-reperfusion injury by the inhibition of oxidative stress and NLRP3-mediated pyroptosis in rats","volume":"272","author":"Nie","year":"2021","journal-title":"Life Sci."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/20\/3271\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:56:09Z","timestamp":1760144169000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/20\/3271"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,18]]},"references-count":122,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["cells11203271"],"URL":"https:\/\/doi.org\/10.3390\/cells11203271","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,18]]}}}